NCT04592874已完成2 期
A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of AL002 in Participants With Early Alzheimer's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Alector Inc.
- 入组人数
- 356
- 试验地点
- 87
- 主要终点
- Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score
研究概览
简要总结
A phase 2 randomized, double blind, placebo controlled study evaluating the efficacy and safety of AL002 in participants with Early Alzheimer's Disease.
详细描述
This is a phase 2 randomized, double blind, placebo controlled study evaluating the efficacy and safety of AL002 administered intravenously in participants with Early Alzheimer's Disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Early AD including evidence of brain amyloidosis by CSF or PET
- •MMSE score ≥ 20 points, CDR Global Score of 0.5 - 1.0, and RBANS score on the DMI ≤
- •Study partner who consents to study participation and who cares for/visits the participant at least 10 hours a week
- •Written informed consent must be obtained and documented (from the participant or, where jurisdictions allow it, from their legal decision maker).
排除标准
- •Dementia due to a condition other than AD including, but not limited to, FTD, Parkinson's disease, dementia with Lewy bodies, Huntington disease, or vascular dementia.
- •Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
- •Current uncontrolled hypertension, diabetes mellitus or thyroid disease. Clinically significant heart disease, liver disease or kidney disease.
- •History or evidence of clinically significant brain disease other than AD.
- •Females who are pregnant or breastfeeding, or planning to conceive within the study period.
- •Any experimental vaccine or gene therapy.
- •History of unresolved cancer.
- •Current use of anticoagulant medications.
- •Residence in a skilled nursing facility, convalescent home, or long term care facility at screening; or requires continuous nursing care.
- •Participant is positive for presence of APOE e4/e4 genotype.
研究组 & 干预措施
AL002 Dose 3
Experimental
AL002 every 4 weeks
干预措施: AL002 (Drug)
Placebo
Placebo Comparator
Placebo every 4 weeks
干预措施: Placebo (Drug)
AL002 Dose 1
Experimental
AL002 every 4 weeks
干预措施: AL002 (Drug)
AL002 Dose 2
Experimental
AL002 every 4 weeks
干预措施: AL002 (Drug)
结局指标
主要结局
Disease Progression as Measured by the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score
时间窗: Study completion up to 96 weeks
Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) score at Weeks 24, 48, 72 and 96. The CDR-SB is a tool used to measure disease severity in Alzheimer's disease. This scale assesses three domains of cognition and three domains of function. The domains are rated on a 5 point scale in which the higher the score corresponds to greater cognitive impairment. The scale range is from 0 to 18 where 0 is considered normal and 18 indicates severe dementia.
次要结局
- Change in Mini-Mental Status Examination (MMSE) Score(Study completion up to 96 weeks)
- Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score(Study completion up to 96 weeks)
- Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score(Study completion up to 96 weeks)
- Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living - Mild Cognitive Impairment (ADCS-ADL-MCI) Score(Study completion up to 96 weeks)
- Change in Alzheimer's Disease Composite Score (ADCOMS) Score(Study completion up to 96 weeks)
研究者
研究点 (87)
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相关资讯
Calibrating Microglia States in Alzheimer's Disease: From Anti-Amyloid Antibodies to Multi-Target Microenvironment Protection- Anti-Aβ monoclonal antibodies lecanemab and donanemab provide statistically significant disease modification but offer only modest cognitive benefit and carry ARIA risks, underscoring that amyloid clearance alone is insufficient.
- Microglia are now recognized as central determinants of AD susceptibility and progression, existing along dynamic continua shaped by the TREM2–APOE axis, complement-mediated synaptic pruning, and immunometabolic reprogramming.
- The phase II failure of the TREM2 agonist AL002 illustrates that receptor activation alone cannot overcome broader network dysfunction when lipid overload, complement dysregulation, and metabolic exhaustion are advanced.
- Future therapeutic strategies should combine pathology clearance with microenvironment protection through biomarker-guided, stage-dependent "escort" combination therapies that recalibrate microglial states rather than broadly suppress inflammation.3 months agoAlector's AL002 Fails to Meet Primary Endpoint in Phase 2 Alzheimer's Trial- Alector Therapeutics' AL002, an experimental antibody designed to activate microglia, failed to slow disease progression in a Phase 2 trial for early Alzheimer's disease.
- The INVOKE-2 trial, involving 381 participants, did not demonstrate significant treatment effects on secondary clinical, functional endpoints, or Alzheimer's fluid biomarkers.
- Following the negative results, Alector is discontinuing the long-term extension trial for AL002 and laying off 17% of its workforce to focus on partnered monoclonal antibody programs.
- Alector plans to focus on its collaboration with GSK, including the Phase III INFRONT-3 trial evaluating latozinemab for frontotemporal dementia, with results expected in late 2025/early 2026.last yearAlector Presents Baseline Data from INVOKE-2 Phase 2 Trial of AL002 for Early Alzheimer's Disease• Alector presented baseline characteristics from the INVOKE-2 Phase 2 trial of AL002, a novel TREM2 agonist, at the Alzheimer's Association International Conference (AAIC) 2024.
• The INVOKE-2 trial enrolled 381 participants with early Alzheimer's disease, showing a median age of 71 years and confirming amyloid positivity in all participants.
• Treatment-emergent brain MRI changes (ARIA) were observed, with higher incidence and severity in APOE e4 homozygous carriers, leading to their early discontinuation from the trial.
• Results from the INVOKE-2 trial are expected in the fourth quarter of 2024, with a long-term extension study ongoing to assess the long-term effects of AL002.2 years ago